Antibodies directed to pig non-Gal antigens in naïve and sensitized baboons.
Publication/Presentation Date
9-1-2006
Abstract
BACKGROUND: As pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) are available, primate antibodies to pig non-Gal antigens can be studied.
METHODS: Sera from 56 baboons were tested for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs by flow cytometry. Complement-dependent cytotoxicity was measured in 39 sera. Antibody and cytotoxicity responses were measured in two baboons exposed to a GT-KO pig heart, one not immunosuppressed and one that received only cobra venom factor.
RESULTS: IgM and IgG bound to 95% and 79% of WT PBMC, and 32% and 9% GT-KO PBMC, respectively (WT vs. GT-KO, P< 0.01). Whereas 97% of sera were cytotoxic to WT PBMC, only 64% were cytotoxic to GT-KO PBMC, and the level of cytotoxicity was less (mean 60% vs. 25% lysis, P< 0.05). In the two baboons exposed to GT-KO hearts, anti-non-Gal antibodies increased markedly, peaking after 2 (IgM) and 3 (IgG) weeks, associated with an increase in lysis of GT-KO PBMC.
CONCLUSIONS: Two-thirds of baboon sera demonstrated cytotoxicity to GT-KO PBMC. After GT-KO organ transplantation, if an elicited antibody response develops, it is likely to cause rapid graft rejection.
Volume
13
Issue
5
First Page
400
Last Page
407
ISSN
0908-665X
Published In/Presented At
Ezzelarab, M., Hara, H., Busch, J., Rood, P. P., Zhu, X., Ibrahim, Z., Ball, S., Ayares, D., Awwad, M., & Cooper, D. K. (2006). Antibodies directed to pig non-Gal antigens in naïve and sensitized baboons. Xenotransplantation, 13(5), 400–407. https://doi.org/10.1111/j.1399-3089.2006.00320.x
Disciplines
Medicine and Health Sciences
PubMedID
16925663
Department(s)
Department of Surgery
Document Type
Article